Amino Acids & Proteins MCAT Practice Question
A 34-year-old woman with a history of recurrent bacterial infections undergoes genetic testing, which reveals a mutation in the CTSC gene encoding cathepsin C, a serine protease critical for immune cell function. Structural analysis of the mutant enzyme shows a catalytic triad of serine, histidine, and aspartate residues in the active site. The mutant histidine residue exhibits an abnormally elevated pKa of 7.5 compared to the wild-type pKa of 6.0. This altered pKa impairs the histidine's ability to function as a general base during proteolytic catalysis. Which of the following best explains the increased pKa of the mutant histidine residue?
Answer choices
- APlacement within a hydrophobic microenvironment that reduces the stabilization of the charged imidazolium formCorrect answer
- BLoss of a nearby negatively charged residue that previously stabilized the imidazole through electrostatic interactions
- CIntroduction of a positively charged amino acid adjacent to the histidine, destabilizing its protonated form
- DDisplacement of the histidine from hydrogen bonding networks that normally favor the protonated state
- EPost-translational phosphorylation of a nearby serine residue, creating a local positive charge
- FDirect hydrogen bonding from the catalytic aspartate to the histidine nitrogen, stabilizing the protonated imidazolium
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